Myelofibrosis
Conditions
Brief summary
This is a single site, open-label, dose de-escalation, Phase 1 study of pegylated interferon alfa-2a administered after alloHCT in subjects with primary or secondary myelofibrosis. Part 1 of the study will assess the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period and identify the Recommended Phase 2 Dose (RP2D). Once the RP2D is identified, 6 additional patients will be enrolled in the expansion cohort.
Interventions
PegINFa will be given once every 2 weeks by subcutaneous administration in the abdomen or thigh.
Sponsors
University of Utah
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Pre-Transplant Inclusion Criteria (Step 1) * Male or female subject aged ≥ 18 years. * Diagnosis of primary or secondary myelofibrosis. * Eligible to undergo a myeloablative or reduced intensity conditioning regimen (MAC or RIC) * Eligible to undergo a standard of care bone marrow biopsy with aspirate as part of his or her routine pre-transplant work-up. * Peripheral blood stem cell (PBSC) graft * 10/10 HLA matched related or matched unrelated donor * ECOG performance status ≤ 2. * For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women \< 50 years of age: * Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and * Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or * Underwent surgical sterilization (bilateral oophorectomy or hysterectomy). * Women ≥ 50 years of age: * Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or * Had radiation-induced menopause with last menses \>1 year ago; or * Had chemotherapy-induced menopause with last menses \>1 year ago; or * Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy). * Female subjects of childbearing potential and male subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception as described in Section 5.4.1. Treatment Inclusion Criteria (Step 2) * Male or female subject aged ≥ 18 years. * Diagnosis of primary or secondary myelofibrosis. * Have undergone a myeloablative or reduced-intensity conditioning regimen (MAC or RIC) and be 50-80 days from Day 0 of transplant at initiation of study therapy. * Peripheral blood stem cell (PBSC) graft * 10/10 HLA matched related or matched unrelated donor * ECOG Performance Status ≤ 2. * Adequate organ function as defined as: * Hepatic: * Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN) * AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN * Renal: * Estimated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula: * TSH and T4 within normal limits or adequately controlled thyroid function. * For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women \< 50 years of age: * Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and * Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or * Underwent surgical sterilization (bilateral oophorectomy or hysterectomy). * Women ≥ 50 years of age: * Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or * Had radiation-induced menopause with last menses \>1 year ago; or * Had chemotherapy-induced menopause with last menses \>1 year ago; or * Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy). * Female subjects of childbearing potential and male subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception as described in Section 5.4.1. * Male subjects must agree to use a condom during intercourse for the duration of study therapy as described in Section 5.4.1. * Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior cancer therapy, unless considered clinically not significant by the treating investigator. * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of dose-limiting toxicities (DLTs) during the DLT evaluation period | Start of treatment to 86 days after treatment initiation | To identify the Recommended Phase 2 Dose (RP2D) of pegylated interferon alfa-2a in subjects undergoing allogeneic hematopoietic cell transplantation for primary or secondary myelofibrosis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the tolerability of pegylated interferon alfa-2a in the study population. | 3 years | Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE version 5.0), seriousness, duration, and relationship to study treatment. |
| Assess the rate of treatment-related mortality in the study population. | 3 years | Rate of treatment-related mortality which is defined as proportion of deaths in patients who have received at least one dose of study therapy, which is attributed to complications from alloHCT or conditioning therapy (in the absence of myelofibrosis relapse) from 30 days after the end of conditioning therapy to one week after the last dose of study therapy. |
| Assess the safety of pegylated interferon alfa-2a in the study population. | 3 years | Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE version 5.0), seriousness, duration, and relationship to study treatment. |
| Assess the incidence of acute and/or chronic graft versus host disease (GVHD) in the study population | 3 years | Cumulative incidence of Glucksberg grade II, III, and IV acute GVHD and incidence of mild, moderate or severe chronic GVHD per NIH grading criteria. |
| Assess Objective Response Rate (ORR) in the study population. | 3 Years | Response rates according to IWG-MRT including, CR, PR, CI, PD, SD, or Relapse. |
| Assess leukemia-free survival (LFS) in the study population. | 3 years | Rate of Leukemia-free survival (LFS) as defined from the day of allogeneic hematopoietic cell transplantation to the time documented disease relapse/progression (date of bone marrow blast count of 20% or greater or date of first peripheral blast count of 20% or greater that was subsequently confirmed to sustain for at least 8 weeks), initiation of non-protocol MF therapy, loss to follow-up, study end, or death from any cause, whichever comes first. |
Countries
United States
Contacts
Primary ContactCatherine Cromar
Outcome results
None listed